TRIM63 and ischemia: This complex nature of UPS-mediated reactions to cardiac stress is marvelously illustrated by contrasting works from Willis and colleagues: on the one hand transgenic overexpression of MuRF-1 mediates cardioprotective effects in models of ischemia, on the other hand MuRF-1 transgenic mice demonstrate progressive decline in cardiac function as well as increased susceptibility to TAC-induced heart failure (Willis et al., 2007, 2009b).